Trial of Dasatinib in Advanced Sarcomas

Sponsor
Sarcoma Alliance for Research through Collaboration (Other)
Overall Status
Completed
CT.gov ID
NCT00464620
Collaborator
Bristol-Myers Squibb (Industry)
366
Enrollment
20
Locations
1
Arm
120
Duration (Months)
18.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will examine the response rate and the 6-month progression-free survival rates of subjects with advanced sarcoma treated with dasatinib.

Detailed Description

Further details provided by SARC (Sarcoma Alliance for Research through Collaboration):

Treatment: Subjects take Dasatinib twice daily by mouth for 28 days per 28 day cycle.

Subjects will be seen for interim medical history, physical exam and laboratory studies prior to each cycle. Subjects will undergo tumor imaging every 2 months (8 weeks) for the first 6 months and approximately every 3 months thereafter while on treatment.

A blood sample for collection of specimens with which to later study serum level of Dasatinib and effects on biomarkers of drug activity will be obtained approximately 2 to 4 weeks after the start of treatment.

Central collection of archival tumor with which to later study the frequency of expression and/or mutation of kinases inhibited by dasatinib will occur.

Subjects will be followed for approximately every 3 months until 2 years from registration and then approximately yearly until 5 years from registration.

Study Design

Study Type:
Interventional
Actual Enrollment :
366 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial of Dasatinib in Advanced Sarcomas
Study Start Date :
May 1, 2007
Actual Primary Completion Date :
Dec 1, 2016
Actual Study Completion Date :
May 1, 2017

Arms and Interventions

ArmIntervention/Treatment
Experimental: Dasatinib, 70 mg, twice daily

Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles

Drug: Dasatinib
oral agent, continuous dosing, Cycles = 28 days

Outcome Measures

Primary Outcome Measures

  1. Response Rate: Number of Participants With Objective Tumor Response [Up to 24 months]

    Assessment of objective tumor response for response rate with MRI or CT using Choi criteria: Complete Remission (CR) Complete disappearance of all measurable and evaluable disease for at least 4 weeks; Partial Remission (PR) A 10% or greater decrease from the baseline in the sum of the largest diameters of all measurable target lesions.

  2. 6 Month Progression-free Survival Rate of "Indolent" Sarcomas Treated With Dasatinib [At 6 months]

    Estimate the 6 month progression-free survival rate of "indolent" sarcomas treated with dasatinib. Progression is defined using Choi criteria, as a 10% or greater increase in the sum of all measurable target lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or unequivocal reappearance of any lesion which had disappeared, or appearance of any new lesions of greater than double slice thickness in size, or any new or enlarging solid nodule in a previously hypodense treated mass.

  3. 6 Month Progression-free Survival Rate of Gastrointestinal Stromal Tumors (GIST) [6 months]

    To estimate the 6 month progression-free survival rate of gastrointestinal stromal tumors (GIST). Progression is defined using Choi criteria, as a 10% or greater increase in the sum of all measurable target lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or unequivocal reappearance of any lesion which had disappeared, or appearance of any new lesions of greater than double slice thickness in size, or any new or enlarging solid nodule in a previously hypodense treated mass.

Secondary Outcome Measures

  1. Median Time-to-progression of Subjects With GIST Treated With Dasatinib. [Up to 30 months]

    To estimate the median time-to-progression of subjects with GIST treated with dasatinib.

  2. Overall Survival Rates at 2 and 5 Years From Registration of Subjects Treated With Dasatinib. [At 2 and 5 years]

    To estimate the overall survival rates at 2 and 5 years from registration of subjects treated with dasatinib.

  3. Median Time-to-progression of Subjects With "Indolent" Sarcomas Treated With Dasatinib. [Up to 24 months]

    To estimate the median time-to-progression of subjects with "indolent" sarcomas treated with dasatinib.

  4. 6 Month Progression-free Survival Rate of Subjects Enrolled in the Aggressive Subtype. [At 6 months]

    To estimate the 6 month progression-free survival rate of subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade chondrosarcomas, Ewing's sarcoma, Malignant fibrous histiocytoma (MFH), rhabdomyosarcoma and MPNST treated with dasatinib.

  5. Median Time-to-progression of Subjects Enrolled in the Aggressive Subtype. [Up to 37 weeks]

    To estimate the median time-to-progression of subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade chondrosarcomas, Ewing's sarcoma, MFH, rhabdomyosarcoma and MPNST treated with dasatinib.

  6. Overall Survival Rates at 2 and 5 Years From Registration of Subjects Enrolled in the Aggressive Subtype Treated With Dasatinib. [At 2 and 5 years]

    To estimate the overall survival rates at 2 and 5 years from registration of subjects enrolled in the aggressive subtype treated with dasatinib.

  7. Uni-dimensional and Bi-dimensional Tumor Size, Tumor Volumes and Tumor Average Density Determined by Computer-aided Automated Detection in a Subset of Subjects With Tumor Predominately Involving the Lung [Up to 37 weeks]

    To prospectively collect uni-dimensional and bi-dimensional tumor size, tumor volumes and tumor average density determined by computer-aided automated detection in a subset of subjects with tumor predominately involving the lung

  8. Plasma Level of Dasatinib and Inhibition of SRC and/or Focal Adhesion Kinase (FAK) in Peripheral Blood Mononuclear Cells [2-4 weeks from start of treatment]

    Obtain blood samples to characterize plasma level of dasatinib and inhibition of SRC and/or FAK in peripheral blood mononuclear cells 2 hours after ingestion of drug at 2-4 weeks from the start of treatment if activity of the drug in a sarcoma subtype warrants further study.

  9. Number of Participants With Tumors With Kinase Expression [Up to 37 weeks]

    Obtain tumor tissue for creation of tissue microarrays to examine the frequency of kinase expression such as SRC and/or FAK in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, Alveolar soft part sarcoma (ASPS), chordoma, epithelioid sarcoma, giant cell tumor of bone, hemangiopericytoma, and GIST if activity of the drug in a subtype warrants further study. The outcome measure demonstrates the number of participants who had tissue that was able to generate tissue microarray for kinase expression.

  10. Number of Participants With Tumors With Mutations in Kinases [Up to 37 weeks]

    Obtain tumor tissue to examine the frequency of mutations in kinases such as PDGFR in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, ASPS, chordoma, epithelioid sarcoma, giant cell tumor of bone, hemangiopericytoma and GIST if activity of the drug in a subtype warrants further study. The outcome measure demonstrates the tissue that was able to generate tissue microarray for PDGFR analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:
13 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Unresectable, recurrent, or metastatic histologically-confirmed soft tissue or bone sarcoma of one of the following subtypes:
  • Leiomyosarcoma --* NO LONGER ELIGIBLE*

  • Liposarcoma--* NO LONGER ELIGIBLE*

  • Malignant fibrous histiocytoma (MFH)/pleomorphic undifferentiated sarcoma--* NO LONGER ELIGIBLE*

  • Rhabdomyosarcoma --* NO LONGER ELIGIBLE*

  • Malignant peripheral nerve sheath tumor (MPNST) --* NO LONGER ELIGIBLE*

  • Osteosarcoma (skeletal or extraosseous)--* NO LONGER ELIGIBLE*

  • Ewing's --* NO LONGER ELIGIBLE*

  • Chondrosarcoma

  • Alveolar soft part sarcoma

  • Chordoma

  • Epithelioid sarcoma

  • Giant cell tumor of bone

  • Hemangiopericytoma/solitary fibrous tumor

  • Gastrointestinal Stromal Tumor (GIST) --* NO LONGER ELIGIBLE*

  1. Documentation that subjects with leiomyosarcoma, liposarcoma, osteosarcoma, Ewing's, MPNST, rhabdomyosarcoma or MFH have received, not been eligible for or refused at least one prior chemotherapy regimen before participation in the dasatinib study. Subjects with GIST must have received or been intolerant to imatinib; prior treatment with other agents including sunitinib is not required.Neoadjuvant/adjuvant chemotherapy qualifies as prior therapy.

  2. Subjects must have unidimensionally measurable lesion(s) either by x-ray, computed tomography (CT), magnetic resonance imaging (MRI) or physical examination documented within 30 days prior to registration.

  3. Prior radiation will be allowed. More than two weeks should have elapsed since the administration of the last fraction of radiation therapy, and subjects must have recovered from grade 2 or higher associated toxicities. Measurable lesions, which are selected as target lesions, must be outside previously radiated fields or have documented progression no sooner than 6 weeks after completion of radiation.

  4. More than 2 weeks must have elapsed since the subject has received any prior systemic chemotherapy (6 weeks for mitomycin C), and the patient should have recovered from toxicities to the baseline prior to the last course of chemotherapy.

  5. Adequate hematologic function within 14 days prior to registration.

  6. Prothrombin Time (PT) (or INR) and Partial Thromboplastin Time (PTT) ≤ 1.5 times the institutional upper limit of normal (ULN) within 14 days prior to registration.

  7. Serum creatinine ≤ 2.0 times the institutional ULN within 14 days prior to registration.

  8. Serum magnesium, potassium and adjusted (or ionized) calcium ≥ the institutional lower limit of normal (LLN). (Supplementation of electrolytes prior to screening is allowed).

  9. Left ventricular ejection fraction ≥ 45% measured by echocardiogram or multiple gated acquisition (MUGA) within 30 days prior to registration (but must be performed after the last dose of an anthracycline) for subjects who have received an anthracycline (e.g. doxorubicin, epirubicin) or have a medical history of cardiac disease. The measurement of left ventricular ejection fraction is not required of subjects whom have not received cardiotoxic chemotherapy (e.g. anthracycline) and do not have a medical history of cardiac disease.

  10. Sexually active women and men of childbearing potential must agree to use an effective method of birth control during the course of the study and for up to 3 months following the last dose of the study drug, in a manner such that risk of pregnancy is minimized. Surgical sterilization, intrauterine device or barrier method (e.g. condom and/or diaphragm with spermicidal agents) are acceptable forms of birth control.

  11. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to treatment. A pregnancy test is not required for registration. Women who have not menstruated for more than 2 years will be considered postmenopausal, thus not of childbearing potential.

  12. Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.

  13. Weight ≥ 50 kg because there is limited experience with dasatinib in subjects weighing less than 50 kg.

  14. ≥13 years of age Minors will be required to sign an assent document prior to treatment.

  15. Subjects must be able to swallow whole tablets.

  16. Subjects must be informed of the investigational nature of the study and provide written, informed consent and authorization to release protected health information using a document(s) approved by the investigator's institution.

  17. A paraffin block, either from a previous surgery or recent biopsy, should be available for correlative studies. If a block of tumor is not available, at least 8 unstained slides of tumor sample, 1 H&E and three (3) 15 micron-thick sections in an eppendorf tube for DNA extraction from a representative portion of the sarcoma may be substituted after discussion with and approval from the study Principal Investigator.

Exclusion Criteria:
  1. Subjects who are curable by conventional multidisciplinary management.

  2. Subjects with symptomatic central nervous system metastasis.

  3. Women who are pregnant or nursing/breastfeeding.

  4. History of significant bleeding disorder unrelated to cancer, including:

  • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

  • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)

  1. Subjects currently taking medications that inhibit platelet function (i.e., aspirin, dipyridamole, epoprostenol, eptifibatide, clopidogrel, cilostazol, abciximab, ticlopidine, and any non-steroidal anti-inflammatory drug) because of a potential increased risk of bleeding from dasatinib.

  2. Subjects currently taking anticoagulants (warfarin, heparin/low molecular weight heparin [e.g., danaparoid, dalteparin, tinzaparin, enoxaparin]) because of a potential increased risk of bleeding from dasatinib.

  3. Diagnosis of unstable angina or myocardial infarction within 6 months of study entry.

  4. Subjects currently taking one or more of the following drugs that are generally accepted to have a risk of causing Torsades de Pointes:

  • Quinidine, procainamide, disopyramide

  • Amiodarone, sotalol, ibutilide, dofetilide

  • Erythromycins, clarithromycin

  • Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

  • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.

  1. Diagnosed or suspected congenital long QT syndrome.

  2. Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec) within 30 days prior to study registration.

  3. Subjects unable or unwilling to suspend treatment with bisphosphonates for at least the first 8 weeks of treatment with study drug because of the risk of hypocalcemia caused by dasatinib.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Arkansas Children's HospitalLittle RockArkansasUnited States72202
2City of HopeDuarteCaliforniaUnited States91010
3Cedars-Sinai Outpatient Cancer CenterLos AngelesCaliforniaUnited States90048
4Stanford UniversityPalo AltoCaliforniaUnited States94304
5Sarcoma Oncology CenterSanta MonicaCaliforniaUnited States90403
6Washington Cancer InstituteWashingtonDistrict of ColumbiaUnited States20010
7Winship Cancer Institute at Emory UniversityAtlantaGeorgiaUnited States30308
8Kootenai Cancer CenterCoeur d'AleneIdahoUnited States83814
9Oncology SpecialistsPark RidgeIllinoisUnited States60068
10Indiana University Cancer CenterIndianapolisIndianaUnited States46202
11University of Iowa Hospitals and ClinicsIowa CityIowaUnited States52242
12Johns Hopkins Sidney Kimmel Comprehensive Cancer CenterBaltimoreMarylandUnited States21231
13Massachusetts General HospitalBostonMassachusettsUnited States02114
14Dana Farber Cancer InstituteBostonMassachusettsUnited States02115
15University of MichiganAnn ArborMichiganUnited States48109
16Nebraska Methodist HospitalOmahaNebraskaUnited States68114
17Pennsylvania Oncology Hematology AssociatesPhiladelphiaPennsylvaniaUnited States19106
18Fox Chase Cancer CenterPhiladelphiaPennsylvaniaUnited States19111
19University of Pittsburgh Cancer InstitutePittsburghPennsylvaniaUnited States15232
20MD AndersonHoustonTexasUnited States77030

Sponsors and Collaborators

  • Sarcoma Alliance for Research through Collaboration
  • Bristol-Myers Squibb

Investigators

  • Principal Investigator: Scott Schuetze, MD, PhD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier:
NCT00464620
Other Study ID Numbers:
  • SARC009
First Posted:
Apr 23, 2007
Last Update Posted:
Nov 23, 2018
Last Verified:
Oct 1, 2018

Study Results

Participant Flow

Recruitment Details50 patients with GIST were enrolled between June 2008 and December 2009 and 48 were evaluable for response. Between May 2007 and May 2009, 200 patients with advanced, high-grade sarcoma were enrolled into the aggressive subtype for this study. 116 patients were registered beginning in July 2007 to the indolent subtype for this study.
Pre-assignment Detail
Arm/Group TitleGIST: Dasatinib, 70 mg, Twice DailyAggressive Subtypes: Dasatinib, 70 mg, Twice DailyIndolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Period Title: Overall Study
STARTED50200116
COMPLETED48198109
NOT COMPLETED227

Baseline Characteristics

Arm/Group TitleDasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Overall Participants359
Age (years) [Median (Full Range) ]
Aggressive subtype
52
GIST
60
Indolent
54
Sex: Female, Male (Count of Participants)
Female
96
26.7%
Male
104
29%
Female
19
5.3%
Male
31
8.6%
Female
33
9.2%
Male
76
21.2%
Race/Ethnicity, Customized (Count of Participants)
White
171
47.6%
Black
15
4.2%
Asian
6
1.7%
Other
6
1.7%
Unknown
2
0.6%
Native American
0
0%
White
41
11.4%
Black
3
0.8%
Asian
3
0.8%
Other
1
0.3%
Unknown
1
0.3%
Native American
1
0.3%
White
94
26.2%
Black
8
2.2%
Asian
3
0.8%
Other
4
1.1%
Unknown
0
0%
Native American
0
0%

Outcome Measures

1. Primary Outcome
TitleResponse Rate: Number of Participants With Objective Tumor Response
DescriptionAssessment of objective tumor response for response rate with MRI or CT using Choi criteria: Complete Remission (CR) Complete disappearance of all measurable and evaluable disease for at least 4 weeks; Partial Remission (PR) A 10% or greater decrease from the baseline in the sum of the largest diameters of all measurable target lesions.
Time FrameUp to 24 months

Outcome Measure Data

Analysis Population Description
116 subjects enrolled in the Indolent subtype, however 109 subjects began treatment. 50 patients enrolled in the GIST subtype, however 48 patients were evaluable. This explains the discrepancy between Overall Number of Participants Analyzed.
Arm/Group TitleGIST: Dasatinib, 70 mg, Twice DailyAggressive Subtypes: Dasatinib, 70 mg, Twice DailyIndolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants48198109
Count of Participants [Participants]
12
3.3%
14
NaN
20
NaN
2. Primary Outcome
Title6 Month Progression-free Survival Rate of "Indolent" Sarcomas Treated With Dasatinib
DescriptionEstimate the 6 month progression-free survival rate of "indolent" sarcomas treated with dasatinib. Progression is defined using Choi criteria, as a 10% or greater increase in the sum of all measurable target lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or unequivocal reappearance of any lesion which had disappeared, or appearance of any new lesions of greater than double slice thickness in size, or any new or enlarging solid nodule in a previously hypodense treated mass.
Time FrameAt 6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleIndolent Subtypes: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants109
Count of Participants [Participants]
52
14.5%
3. Primary Outcome
Title6 Month Progression-free Survival Rate of Gastrointestinal Stromal Tumors (GIST)
DescriptionTo estimate the 6 month progression-free survival rate of gastrointestinal stromal tumors (GIST). Progression is defined using Choi criteria, as a 10% or greater increase in the sum of all measurable target lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or unequivocal reappearance of any lesion which had disappeared, or appearance of any new lesions of greater than double slice thickness in size, or any new or enlarging solid nodule in a previously hypodense treated mass.
Time Frame6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleGIST: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants48
Count of Participants [Participants]
14
3.9%
4. Secondary Outcome
TitleMedian Time-to-progression of Subjects With GIST Treated With Dasatinib.
DescriptionTo estimate the median time-to-progression of subjects with GIST treated with dasatinib.
Time FrameUp to 30 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleGIST: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants48
Median (Full Range) [months]
2.9
5. Secondary Outcome
TitleOverall Survival Rates at 2 and 5 Years From Registration of Subjects Treated With Dasatinib.
DescriptionTo estimate the overall survival rates at 2 and 5 years from registration of subjects treated with dasatinib.
Time FrameAt 2 and 5 years

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleGIST: Dasatinib, 70 mg, Twice DailyIndolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants48109
2 years overall survival
21
5.8%
48
NaN
5 years overall survival
8
2.2%
14
NaN
6. Secondary Outcome
TitleMedian Time-to-progression of Subjects With "Indolent" Sarcomas Treated With Dasatinib.
DescriptionTo estimate the median time-to-progression of subjects with "indolent" sarcomas treated with dasatinib.
Time FrameUp to 24 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleIndolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants109
Median (Full Range) [months]
5.8
7. Secondary Outcome
Title6 Month Progression-free Survival Rate of Subjects Enrolled in the Aggressive Subtype.
DescriptionTo estimate the 6 month progression-free survival rate of subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade chondrosarcomas, Ewing's sarcoma, Malignant fibrous histiocytoma (MFH), rhabdomyosarcoma and MPNST treated with dasatinib.
Time FrameAt 6 months

Outcome Measure Data

Analysis Population Description
The numbers analyzed in one or more rows are different because they are broken up by cohorts.
Arm/Group TitleAggressive Subtypes: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants198
UPS
6
1.7%
Leiomyosarcoma
5
1.4%
Osteosarcoma
5
1.4%
Rhabdomyosarcoma
0
0%
Ewing's Sarcoma
1
0.3%
Liposarcoma
0
0%
MPNST
0
0%
8. Secondary Outcome
TitleMedian Time-to-progression of Subjects Enrolled in the Aggressive Subtype.
DescriptionTo estimate the median time-to-progression of subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade chondrosarcomas, Ewing's sarcoma, MFH, rhabdomyosarcoma and MPNST treated with dasatinib.
Time FrameUp to 37 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleAggressive Subtypes: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants198
Median (Full Range) [months]
1.9
9. Secondary Outcome
TitleOverall Survival Rates at 2 and 5 Years From Registration of Subjects Enrolled in the Aggressive Subtype Treated With Dasatinib.
DescriptionTo estimate the overall survival rates at 2 and 5 years from registration of subjects enrolled in the aggressive subtype treated with dasatinib.
Time FrameAt 2 and 5 years

Outcome Measure Data

Analysis Population Description
The number analyzed in one or more rows differs from overall number because the rows are broken down into cohorts. The counts in the categories will not add up to the number analyzed, because those numbers represent number of participants that have reached overall survival at 2 and 5 years.
Arm/Group TitleAggressive Subtypes: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants198
Ewing's Sarcoma : 2 year overall survival rate
7
1.9%
Ewing's Sarcoma : 5 year overall survival rate
0
0%
Leiomyosarcoma : 2 year overall survival rate
21
5.8%
Leiomyosarcoma : 5 year overall survival rate
2
0.6%
Liposarcoma : 2 year overall survival rate
0
0%
Liposarcoma : 5 year overall survival rate
0
0%
MPNST : 2 year overall survival rate
0
0%
MPNST : 5 year overall survival rate
0
0%
Osteosarcoma : 2 year overall survival rate
15
4.2%
Osteosarcoma : 5 year overall survival rate
0
0%
Rhabdomyosarcoma : 2 year overall survival rate
8
2.2%
Rhabdomyosarcoma : 5 year overall survival rate
7
1.9%
UPS : 2 year overall survival rate
26
7.2%
UPS : 5 year overall survival rate
6
1.7%
10. Secondary Outcome
TitleUni-dimensional and Bi-dimensional Tumor Size, Tumor Volumes and Tumor Average Density Determined by Computer-aided Automated Detection in a Subset of Subjects With Tumor Predominately Involving the Lung
DescriptionTo prospectively collect uni-dimensional and bi-dimensional tumor size, tumor volumes and tumor average density determined by computer-aided automated detection in a subset of subjects with tumor predominately involving the lung
Time FrameUp to 37 weeks

Outcome Measure Data

Analysis Population Description
This data was not collected because the imaging software and work station was not obtained.
Arm/Group TitleGIST: Dasatinib, 70 mg, Twice DailyAggressive Subtypes: Dasatinib, 70 mg, Twice DailyIndolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants000
11. Secondary Outcome
TitlePlasma Level of Dasatinib and Inhibition of SRC and/or Focal Adhesion Kinase (FAK) in Peripheral Blood Mononuclear Cells
DescriptionObtain blood samples to characterize plasma level of dasatinib and inhibition of SRC and/or FAK in peripheral blood mononuclear cells 2 hours after ingestion of drug at 2-4 weeks from the start of treatment if activity of the drug in a sarcoma subtype warrants further study.
Time Frame2-4 weeks from start of treatment

Outcome Measure Data

Analysis Population Description
Evaluation of blood levels of drug was not performed because there was insufficient activity and the level of activity did not warrant further study.
Arm/Group TitleGIST: Dasatinib, 70 mg, Twice DailyAggressive Subtypes: Dasatinib, 70 mg, Twice DailyIndolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants000
12. Secondary Outcome
TitleNumber of Participants With Tumors With Kinase Expression
DescriptionObtain tumor tissue for creation of tissue microarrays to examine the frequency of kinase expression such as SRC and/or FAK in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, Alveolar soft part sarcoma (ASPS), chordoma, epithelioid sarcoma, giant cell tumor of bone, hemangiopericytoma, and GIST if activity of the drug in a subtype warrants further study. The outcome measure demonstrates the number of participants who had tissue that was able to generate tissue microarray for kinase expression.
Time FrameUp to 37 weeks

Outcome Measure Data

Analysis Population Description
The overall number of participants analyzed demonstrates the number of participants whose tumor samples received. The results illustrate the tissue that was able to generate tissue microarray for SRC and FAK analysis.
Arm/Group TitleOsteosarcomaLeiomyosarcomaMFH/Undifferentiated Pleomorphic Sarcoma
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants324437
Count of Participants [Participants]
11
3.1%
24
NaN
16
NaN
13. Secondary Outcome
TitleNumber of Participants With Tumors With Mutations in Kinases
DescriptionObtain tumor tissue to examine the frequency of mutations in kinases such as PDGFR in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, ASPS, chordoma, epithelioid sarcoma, giant cell tumor of bone, hemangiopericytoma and GIST if activity of the drug in a subtype warrants further study. The outcome measure demonstrates the tissue that was able to generate tissue microarray for PDGFR analysis.
Time FrameUp to 37 weeks

Outcome Measure Data

Analysis Population Description
The overall number of participants analyzed demonstrates the number of participants whose tumor samples were received. The results illustrate the tissue that was able to generate tissue microarray for PDGFR analysis.
Arm/Group TitleOsteosarcomaLeiomyosarcomaMFH/Undifferentiated Pleomorphic Sarcoma
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 daysPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants324437
Count of Participants [Participants]
11
3.1%
24
NaN
16
NaN

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group TitleGIST, Aggressive, Indolent Subtypes
Arm/Group DescriptionPatients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
All Cause Mortality
GIST, Aggressive, Indolent Subtypes
Affected / at Risk (%)# Events
Total/ (NaN)
Serious Adverse Events
GIST, Aggressive, Indolent Subtypes
Affected / at Risk (%)# Events
Total158/355 (44.5%)
Blood and lymphatic system disorders
Blood-other1/355 (0.3%) 1
Cardiac disorders
Pericardial effusion1/355 (0.3%) 1
Ventricular tachycardia1/355 (0.3%) 1
Cardiac ischemia/infarction1/355 (0.3%) 1
Congestive heart failure2/355 (0.6%) 2
Atrial Fibrillation2/355 (0.6%) 2
Gastrointestinal disorders
Colitis4/355 (1.1%) 4
Constipation4/355 (1.1%) 4
Diarrhea8/355 (2.3%) 11
Distention1/355 (0.3%) 1
Esophagitis1/355 (0.3%) 1
Gastritis1/355 (0.3%) 1
GI Hemorrhage: lower GI2/355 (0.6%) 2
GI Hemorrhage: upper GI2/355 (0.6%) 2
GI Obstruction: small bowel6/355 (1.7%) 6
GI Obstruction: stomach1/355 (0.3%) 1
GI Pain: abdomen12/355 (3.4%) 12
GI Ulcer: colon1/355 (0.3%) 1
GI- other1/355 (0.3%) 1
Nausea18/355 (5.1%) 20
Vomiting17/355 (4.8%) 19
GI Hemorrhage- abdomen1/355 (0.3%) 1
GI Hemorrhage- esophagus1/355 (0.3%) 1
GI Hemorrhage- rectum2/355 (0.6%) 2
GI Hemorrhage- stomach1/355 (0.3%) 1
Pancreatitis1/355 (0.3%) 1
General disorders
Constitutional symptoms-other1/355 (0.3%) 1
Death, NOS4/355 (1.1%) 4
Disease progression, NOS7/355 (2%) 7
Fatigue7/355 (2%) 7
Fever15/355 (4.2%) 16
Flu-like syndrome1/355 (0.3%) 1
Hemorrhage-other2/355 (0.6%) 2
Pain5/355 (1.4%) 5
Sudden death1/355 (0.3%) 1
Multi-organ failure1/355 (0.3%) 1
Rigors/chills1/355 (0.3%) 1
Edema- limb4/355 (1.1%) 4
Gait/walking1/355 (0.3%) 1
Hepatobiliary disorders
Cholecystitis1/355 (0.3%) 1
Immune system disorders
Allergic reaction1/355 (0.3%) 1
Infections and infestations
Infection, Unk ANC: blood2/355 (0.6%) 2
Infection-other5/355 (1.4%) 6
Lung infection, 0-2 ANC: bronchus1/355 (0.3%) 1
Lung Infection, 3-4 ANC: bronchus1/355 (0.3%) 1
Lung Infection, Unk ANC: lung1/355 (0.3%) 1
Injury, poisoning and procedural complications
Fracture3/355 (0.8%) 3
Investigations
ALT2/355 (0.6%) 4
Amylase1/355 (0.3%) 1
AST2/355 (0.6%) 2
Bilirubin1/355 (0.3%) 1
Coagulation-other1/355 (0.3%) 1
Creatinine5/355 (1.4%) 5
Hemoglobin14/355 (3.9%) 15
Leukocytes1/355 (0.3%) 1
Neutrophils2/355 (0.6%) 2
Platelets1/355 (0.3%) 1
Lymphopenia1/355 (0.3%) 1
Metabolism and nutrition disorders
Anorexia4/355 (1.1%) 4
Dehydration11/355 (3.1%) 11
Hyperkalemia2/355 (0.6%) 2
Hyponatremia5/355 (1.4%) 5
Hypokalemia3/355 (0.8%) 3
Lipase1/355 (0.3%) 1
Musculoskeletal and connective tissue disorders
Muscle weakness6/355 (1.7%) 6
Musculo. Pain17/355 (4.8%) 17
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain4/355 (1.1%) 4
Nervous system disorders
CNS hemorrhage4/355 (1.1%) 4
Neuropathy- sensory1/355 (0.3%) 1
Seizure1/355 (0.3%) 1
Syncope1/355 (0.3%) 1
Myelitis1/355 (0.3%) 1
Ataxia1/355 (0.3%) 1
Dizziness1/355 (0.3%) 1
Headache2/355 (0.6%) 2
Psychiatric disorders
Confusion3/355 (0.8%) 3
Anxiety1/355 (0.3%) 1
Renal and urinary disorders
GU Hemorrhage: urinary2/355 (0.6%) 2
GU Hemorrhage: vagina1/355 (0.3%) 1
GU Infection, 0-2 ANC: urinary tract1/355 (0.3%) 1
GU Infection, Unk ANC: ureter1/355 (0.3%) 1
GU Pain: kidney1/355 (0.3%) 1
Incontinence, urinary1/355 (0.3%) 1
Renal failure5/355 (1.4%) 5
Urinary retention1/355 (0.3%) 1
Renal failure7/355 (2%) 7
Reproductive system and breast disorders
Reproductive pain: pelvis1/355 (0.3%) 1
Pelvis pain1/355 (0.3%) 1
Respiratory, thoracic and mediastinal disorders
Aspiration1/355 (0.3%) 1
Dyspnea34/355 (9.6%) 37
Hypoxia5/355 (1.4%) 5
Lung Pain8/355 (2.3%) 8
Pleural effusion30/355 (8.5%) 34
Pneumonitis3/355 (0.8%) 3
Pulmonary-other8/355 (2.3%) 9
Cough2/355 (0.6%) 2
Skin and subcutaneous tissue disorders
Dermatology- other1/355 (0.3%) 1
Rash2/355 (0.6%) 2
Vascular disorders
Hypertension1/355 (0.3%) 1
Hypotension2/355 (0.6%) 2
Thrombosis/embolism6/355 (1.7%) 6
Hypertension2/355 (0.6%) 2
Hypotension4/355 (1.1%) 4
Sweating1/355 (0.3%) 1
Hematoma1/355 (0.3%) 1
Other (Not Including Serious) Adverse Events
GIST, Aggressive, Indolent Subtypes
Affected / at Risk (%)# Events
Total314/355 (88.5%)
Blood and lymphatic system disorders
Thrombocytopenia19/355 (5.4%) 31
Anemia70/355 (19.7%) 103
Petechiae1/355 (0.3%) 1
Lymph node pain1/355 (0.3%) 1
Cardiac disorders
Palpaitations2/355 (0.6%) 2
Prolonged QTc4/355 (1.1%) 4
Pericardial effusion4/355 (1.1%) 4
Cardiac- Other4/355 (1.1%) 5
Atrial Tachycardia1/355 (0.3%) 1
Sinus Bradycardia1/355 (0.3%) 1
Ear and labyrinth disorders
Auditory/Ear- Other1/355 (0.3%) 1
Eye disorders
Dry eye1/355 (0.3%) 1
Blurred vision1/355 (0.3%) 1
Diplopia1/355 (0.3%) 1
Ocular- Other4/355 (1.1%) 5
Eye pain1/355 (0.3%) 1
Gastrointestinal disorders
Constipation27/355 (7.6%) 27
Diarrhea73/355 (20.6%) 99
Nausea81/355 (22.8%) 93
Vomiting36/355 (10.1%) 38
GI Pain: abdomen15/355 (4.2%) 22
Heartburn9/355 (2.5%) 10
Distention3/355 (0.8%) 3
Dehydration5/355 (1.4%) 5
Dry mouth3/355 (0.8%) 3
Taste alteration8/355 (2.3%) 8
Gastritis3/355 (0.8%) 3
Dysphagia4/355 (1.1%) 4
Ascites1/355 (0.3%) 1
Flatulence6/355 (1.7%) 6
Hemorrhoids6/355 (1.7%) 9
Gastrointestinal- Other7/355 (2%) 7
Mucositis4/355 (1.1%) 4
Fistula1/355 (0.3%) 1
GI Hemorrhage9/355 (2.5%) 10
GI Pain15/355 (4.2%) 22
General disorders
Edema34/355 (9.6%) 50
Fatigue113/355 (31.8%) 144
Fever27/355 (7.6%) 29
Pain- Other17/355 (4.8%) 17
Rigors/chills16/355 (4.5%) 18
Flu-like syndrome3/355 (0.8%) 3
Hepatobiliary disorders
Hepatic pain1/355 (0.3%) 1
Immune system disorders
Allergic reaction1/355 (0.3%) 1
Infections and infestations
Lung Infection14/355 (3.9%) 16
GU Infection4/355 (1.1%) 4
GI Infection8/355 (2.3%) 11
Skin Infection1/355 (0.3%) 1
Eye Infection1/355 (0.3%) 1
Injury, poisoning and procedural complications
Bruising2/355 (0.6%) 2
Wound complication1/355 (0.3%) 1
Investigations
Weight loss17/355 (4.8%) 17
Elevated PTT3/355 (0.8%) 4
Leukopenia13/355 (3.7%) 19
Neutropenia15/355 (4.2%) 28
Lymphopenia11/355 (3.1%) 12
Metabolism and nutrition disorders
Anorexia45/355 (12.7%) 49
Hyperglycemia25/355 (7%) 41
Hyponatremia14/355 (3.9%) 18
Hypernatremia1/355 (0.3%) 1
Elevated Alkaline phosphatase15/355 (4.2%) 15
Elevated ALT7/355 (2%) 9
Elevated AST7/355 (2%) 10
Elevated serum bilirubin2/355 (0.6%) 2
Elevated creatinine11/355 (3.1%) 14
Hypoalbuminemia5/355 (1.4%) 5
Hypokalemia6/355 (1.7%) 6
Hyperkalemia6/355 (1.7%) 6
Acidosis1/355 (0.3%) 1
Hypoglycemia2/355 (0.6%) 2
Low serum bicarbonate2/355 (0.6%) 2
Hypocalcemia7/355 (2%) 10
Hypercalcemia3/355 (0.8%) 3
Hypermagnesemia9/355 (2.5%) 10
Elevated lipase1/355 (0.3%) 1
Hypophosphatemia5/355 (1.4%) 7
Musculoskeletal and connective tissue disorders
Muscle weakness7/355 (2%) 8
Musculoskeletal pain67/355 (18.9%) 100
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor Pain10/355 (2.8%) 11
Nervous system disorders
Headache52/355 (14.6%) 68
CNS Hemorrhage2/355 (0.6%) 2
Somnolence1/355 (0.3%) 1
Seizure1/355 (0.3%) 1
Cognitive disturbance1/355 (0.3%) 1
Tremor1/355 (0.3%) 1
Ataxia1/355 (0.3%) 1
Involuntary movement3/355 (0.8%) 3
Sensory neuropathy8/355 (2.3%) 8
Leukoencephalopathy1/355 (0.3%) 1
Dizziness8/355 (2.3%) 10
Psychiatric disorders
Insomnia8/355 (2.3%) 8
Confusion4/355 (1.1%) 4
Agitation3/355 (0.8%) 3
Anxiety4/355 (1.1%) 5
Depression7/355 (2%) 8
Renal and urinary disorders
Urinary incontinence1/355 (0.3%) 1
Cystitis1/355 (0.3%) 1
Urinary retention2/355 (0.6%) 2
Urinary frequency4/355 (1.1%) 4
Urine color change1/355 (0.3%) 1
Bladder spasms2/355 (0.6%) 2
Renal - Other5/355 (1.4%) 5
Ureter obstruction1/355 (0.3%) 1
GU Hemorrhage3/355 (0.8%) 5
Reproductive system and breast disorders
Pelvis pain4/355 (1.1%) 4
Breast pain2/355 (0.6%) 2
Respiratory, thoracic and mediastinal disorders
Cough45/355 (12.7%) 55
Dyspnea56/355 (15.8%) 78
Pleural effusion43/355 (12.1%) 60
Atelectasis1/355 (0.3%) 1
Hypoxia1/355 (0.3%) 1
Pneumonitis1/355 (0.3%) 1
Voice alteration4/355 (1.1%) 4
Pulmonary- Other9/355 (2.5%) 12
Lung Pain17/355 (4.8%) 18
Skin and subcutaneous tissue disorders
Rash52/355 (14.6%) 64
Urticaria1/355 (0.3%) 2
Pruritus5/355 (1.4%) 5
Acne3/355 (0.8%) 3
Hyperpigmentation1/355 (0.3%) 1
Hypopigmentation3/355 (0.8%) 3
Alopecia2/355 (0.6%) 2
Skin pain1/355 (0.3%) 1
Dermatology- Other8/355 (2.3%) 9
Vascular disorders
Hypertension5/355 (1.4%) 6
Hot flashes3/355 (0.8%) 4
Sweating8/355 (2.3%) 9
Flushing5/355 (1.4%) 5
Phlebitis1/355 (0.3%) 1
Thrombosis/embolism1/355 (0.3%) 1
Vascular- Other1/355 (0.3%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleSARC
OrganizationSARC
Phone(734) 930-7600
Emailsarc@sarctrials.org
Responsible Party:
Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier:
NCT00464620
Other Study ID Numbers:
  • SARC009
First Posted:
Apr 23, 2007
Last Update Posted:
Nov 23, 2018
Last Verified:
Oct 1, 2018